It is challenging to improve the low-temperature catalytic activity and water resistance of manganese oxide for CO oxidation. Herein, Sn is successfully doped into manganese octahedral molecular sieve (OMS-2) by hydro -thermal synthesis. The doping of Sn promotes the low-temperature activity and water resistance of OMS-2 catalysts, and the OMS-5Sn catalyst exhibits the best performance for CO oxidation, which T90 under dry and humid condition are 100 degrees C and 179 degrees C, respectively. According to the results of CO-TPR, O2-TPD, XPS, FT-IR, and ex situ/in situ Raman, the appropriate Sn doping increases the oxygen vacancies and enhances the surface hydrophilicity. Furthermore, the H218O isotope experiment reveals that water can participates in CO oxidation with a surface hydroxyl-mediated Mars-Van Krevelen reaction pathway. Significantly, the study improves the catalytic activity of manganese oxide for CO oxidation and could provide a new proposal to design the water-resistant catalysts incatalytic oxidation reaction.